Fri Nov 11 2022

73 articles - From Friday Nov 04 2022 to Friday Nov 11 2022

parm_toc.knit

Guidelines

Guidelines and related publications, position statements, white papers, technical reviews, consensus statements, etc…


Meta-analysis

meta-analyses and systematic reviews

Lancet Haematol

Second primary malignancies in patients with haematological cancers treated with lenalidomide: a systematic review and meta-analysis.

Further investigations are needed to improve understanding on why lenalidomide only promotes SPM in patients with multiple myeloma. Funding None.

Pubmed   Journal   ReadQx 

Thromb Haemost

Mortality of Escalation and Modulation Antithrombotic Therapy in Coronary Artery Disease Patients: A Meta-analysis of Randomized Controlled Trials.

Either escalation or modulation of ATT has little benefit in all-cause mortality. The variability of the treatment effects on all-cause mortality was mainly attributed to the variability of major or minor bleeding, but not to MI.

Pubmed   Journal   ReadQx 


Original articles

RCT, clinical trials, retrospective studies, etc…

Am J Hematol

Predictors of anemia response to momelotinib therapy in myelofibrosis and impact on survival.

This survival advantage was also noted in transfusion-dependent patients (3.7 vs 1.9years; p=0.01; HR 0.3) and appeared to be restricted to patients with unfavorable genetic profile. The current study suggests short-term survival benefit associated with anemia response in momelotinib treated patients with MF.

Pubmed   Journal   ReadQx 

Blood

EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy.

A large proportion of post-ALL lymphoid neoplasms are associated with an immunodeficient state, likely precipitated by ALL maintenance therapy. Awareness of this underrecognized entity and pertinent diagnostic tests are crucial for early diagnosis and optimal therapy.

Pubmed   Journal   ReadQx 

Genetic basis and molecular profiling in myeloproliferative neoplasms.

Factors that control the conversion from clonal hematopoiesis to MPN include inherited predisposition, presence of additional mutations and inflammation. The complete knowledge of the mutational landscape in individual MPN patients is now increasingly being used to predict outcome and chose the optimal therapy.

Pubmed   Journal   ReadQx 

How I treat thrombotic microangiopathy in the era of rapid genomics.

By taking precedence over a phenotypic approach, an unbiased genomic-focused analysis maximizes the chances of discovering new descriptions related to a given variant. Presented here are four cases of TMA which highlight these issues and substantiate the promise of fast-track genomic sequencing.

Pubmed   Journal   ReadQx 

Impact of poverty and neighborhood opportunity on outcomes for children treated with CD19-directed CAR T-cell therapy.

Investigation of multicenter outcomes and access disparities outside of clinical-trial settings is warranted. Clinical trials: NCT01626495; NCT02435849 ; NCT02374333; NCT02228096; NCT02906371.

Pubmed   Journal   ReadQx 

Lentiviral Gene Therapy for X-Linked Chronic Granulomatous Disease Recapitulates Endogenous CYBB Regulation and Expression.

cepacia infection, and restored healthy donor levels of anti-microbial oxidase activity in neutrophils derived from X-CGD patient HSPCs. Our findings validate the bioinformatics-guided design approach and have yielded a novel lentiviral vector with clinical promise for the treatment of X-CGD.

Pubmed   Journal   ReadQx 

Liver sinusoidal endothelial cells induce BMP6 expression in response to non-transferrin bound iron.

Our data suggest that during systemic iron overload, LSECs internalize NTBI, which promotes oxidative stress and thereby transcriptionally induces Bmp6 via Nrf2. Tfr1 appears to contribute to iron sensing by LSECs mostly under low iron conditions.

Pubmed   Journal   ReadQx 

Natural killer T cells and other innate-like T lymphocytes as emerging platforms for allogeneic cancer cell therapy.

Both unmodified NKTs, which specifically recognize CD1d-bound glycolipid antigens expressed by some types of tumors, and CAR-redirected NKTs are in development as the next generation of allogeneic cell therapy products. In this review, we describe studies on the biology of NKTs and other types of innate-like T cells and summarize experiences in the clinic with unmodified and CAR-redirected NKTs, including recent interim reports on allogeneic NKTs.

Pubmed   Journal   ReadQx 

Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis.

Fitness loss and associated RNA transcriptome and splicing alterations in RXRa; RXRb-deficient HSCs are prevented by Myc haploinsufficiency. Our study reveals the critical importance of RXRs for the maintenance of HSC fitness and their protection from premature aging.

Pubmed   Journal   ReadQx 

Blood Adv

A novel polymer-conjugated human IL-15 improves efficacy of CD19-targeted CAR-T cell immunotherapy.

These data support an ongoing phase I clinical trial of combined CD19 CAR-T and NKTR-255 for R/R B-cell malignancies. This trial is registered at as NCT01865617.

Pubmed   Journal   ReadQx 

Applying CRISPR-Cas9 screens to dissect hematological malignancies.

Specifically, within blood cancers, current CRISPR screens have specifically focused on improving our understanding of drug resistance strategies, disease biology, development of novel therapeutic approaches, and identifying the molecular mechanisms of current therapies, with an underlying aim of improving disease outcomes. Here, we review the development of CRISPR-Cas9 genome editing strategy, explicitly focusing on the recent advances in the CRISPR-Cas9 based screening approaches, its current capabilities, limitations, and future applications in the context of hematological malignancies.

Pubmed   Journal   ReadQx 

Cost-Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Adults with Relapsed or Refractory Follicular Lymphoma.

Under current pricing, CAR-T is unlikely to be cost-effective in unselected FL patients in the third-line setting. Both randomized clinical trials and longer-term clinical follow up can help clarify the benefits of CAR-T and optimal sequencing in patients with FL.

Pubmed   Journal   ReadQx 

Creating an Automated Contemporaneous Cohort in Sickle Cell Anemia to Predict Survival After Disease-Modifying Therapy.

Compared to those receiving no disease-modifying treatment, those treated with hydroxyurea therapy had significantly lower hazard of mortality (hazard ratio=0.38, p=0.016), but no statistical difference for those receiving regular blood transfusions compared to no disease-modifying therapy (hazard ratio=0.71, p=0.440). An automated contemporaneous SCA cohort can be generated to estimate mortality in children and adults with SCA.

Pubmed   Journal   ReadQx 

Downregulated KLF2 in polycythemia vera and essential thrombocythemia induces prothrombotic gene expression.

In PV and ET patients, KLF2 expression was induced by pegylated interferon-a (PegINFa) but not by hydroxyurea treatments. These data suggest that KLF2 may be a regulator of PV and ET thrombosis and a novel therapeutic target to prevent thrombosis.

Pubmed   Journal   ReadQx 

Gata1s mutant mice display persistent defects in the erythroid lineage.

Here we demonstrate that Gata1s mutant mice display macrocytic anemia and features of aberrant megakaryopoiesis throughout life, culminating in profound splenomegaly and bone marrow fibrosis. These data support the use of this animal model for studies of GATA1 deficiencies.

Pubmed   Journal   ReadQx 

Hypodiploidy has Unfavorable Impact on Survival in Pediatric Acute Myeloid Leukemia:An I-BFM Study Group collaboration.

Allogeneic stem cell transplantation (SCT) in first complete remission (CR1) (n=18) did not mitigate the unfavorable outcome of hypodiploidy (adjusted HR for OS was 1.5, p=0.42). We identified pediatric hypodiploid AML as a rare subgroup with an inferior prognosis even in patients treated with SCT in CR1.

Pubmed   Journal   ReadQx 

Low toxicity and excellent outcomes in patients with DLBCL without residual lymphoma at the time of CD19 CAR T-cell therapy.

Our findings suggest that, in patients with R/R DLBCL who have an indication for CAR T-cell therapy, treating patients in complete remission at time of infusion is feasible, safe, and associated with favorable disease control. Further exploration in a larger clinical trial setting is warranted.

Pubmed   Journal   ReadQx 

Outcomes of subsequent neoplasms after umbilical cord blood transplantation in Europe.

In conclusion, despite their poor outcomes, SNs that occur after UCBT are extremely rare. Identification of associated risk factors and early detection may help to improve OS.

Pubmed   Journal   ReadQx 

Pharmacokinetics, pharmacodynamics, safety and efficacy of crizanlizumab in patients with sickle cell disease.

Results here demonstrate the PK/PD properties of crizanlizumab in SCD patients, and the potential sustained efficacy and long-term safety of the drug after >12 months' treatment. This trial is registered at as NCT03264989.

Pubmed   Journal   ReadQx 

Prospective changes of pancreatic iron in patients with thalassemia major and association with chelation therapy.

The reduction in pancreatic iron levels was comparable among the three groups. Our data showed that it is difficult to remove the iron from the pancreas and that the three iron chelators in monotherapy have a comparable efficacy.

Pubmed   Journal   ReadQx 

Reg3a levels at day of allogeneic stem cell transplantation predict outcome and correlate with early antibiotic use.

Reg3a, a known biomarker of acute GI GvHD correlates with intestinal dysbiosis induced by early antibiotic treatment in the period of pretransplant conditioning. Serum concentrations of Reg3a measured on the day of graft infusion are predictive of the risk for TRM of allogenic SCT recipients.

Pubmed   Journal   ReadQx 

The promising efficacy of a risk-based letermovir use strategy in CMV-positive allogeneic hematopoietic cell recipients.

In both risk groups, the two periods were comparable for CMV disease, overall survival, progression-free survival, relapse, and non-relapse mortality. We concluded that a risk-based strategy for letermovir use is an effective strategy which maintains the high efficacy of letermovir in high-risk patients but allows some low-risk patients not to use letermovir.

Pubmed   Journal   ReadQx 

Waldenström Macroglobulinemia Whole Genome Reveals Prolonged Germinal Center Activity and Late Copy Number Aberrations.

In summary, WGS analysis in WM allows the demonstration of sustained germinal center activity over time and allows the reconstruction of the temporal evolution of specific genomic features. In addition, our data suggests that, while MYD88-mutations are central to WM clone establishment and can be observed in precursor disease, CNA may contribute to later phases, and may be used as a biomarker for progression risk from precursor conditions to symptomatic disease.

Pubmed   Journal   ReadQx 

Blood Cancer J

GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms.

The discovery that p300-dependent acetylation regulates GATA-3 mediated transcription by attenuating DNA binding has novel therapeutic implications. As most patients afflicted with GATA-3 driven T-cell neoplasms will succumb to their disease within a few years of diagnosis, these findings suggest opportunities to improve outcomes for these patients.

Pubmed   Journal   ReadQx   PMC

The PIP4K2 inhibitor THZ-P1-2 exhibits antileukemia activity by disruption of mitochondrial homeostasis and autophagy.

The minimal effects of THZ-P1-2 observed in healthy CD34 + cells suggest a favorable therapeutic window. Our study provides insights into the pharmacological inhibition of PIP4K2s targeting mitochondrial homeostasis and autophagy, shedding light on a new class of drugs for acute leukemia.

Pubmed   Journal   ReadQx 

J Hematol Oncol

JMJD4-demethylated RIG-I prevents hepatic steatosis and carcinogenesis.

Decreased RIG-I in HcPCs promotes necroinflammation-induced hepatocarcinogenesis, while increased constitutive methylated RIG-I enhances steatosis and NASH-induced hepatocarcinogenesis. JMJD4-demethylated RIG-I prevents both necroinflammation and NASH-induced hepatocarcinogenesis, which provides mechanistic insight and potential target for preventing HCC.

Pubmed   Journal   ReadQx   PMC

Safe and effective off-the-shelf immunotherapy based on CAR.CD123-NK cells for the treatment of acute myeloid leukaemia.

Our data indicate the feasibility of an innovative off-the-shelf therapeutic strategy based on CAR.CD123-NK cells, characterized by remarkable efficacy and an improved safety profile compared to CAR.CD123-T cells. These findings open a novel intriguing scenario not only for the treatment of refractory/resistant AML patients but also to further investigate the use of CAR-NK cells in other cancers characterized by highly difficult targeting with the most conventional T effector cells.

Pubmed   Journal   ReadQx   PMC

Lancet Haematol

Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial.

Interpretation Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone for induction therapy improved rates of MRD negativity with no new safety signals in patients with newly diagnosed transplantation-eligible multiple myeloma. Funding Sanofi and Bristol Myers Squibb (Celgene).

Pubmed   Journal   ReadQx 

Leukemia

Genetic deletion and pharmacologic inhibition of E3 ubiquitin ligase HOIP impairs the propagation of myeloid leukemia.

Finally, the administration of thiolutin, which inhibits the catalytic activity of Hoip, improved the survival of recipients in murine myeloid leukemia and suppressed propagation in the patient-derived xenograft model of myeloid leukemia. Collectively, these data indicate that inhibition of LUBAC activity may be a valid therapeutic target for myeloid leukemia.

Pubmed   Journal   ReadQx 

Identification and interrogation of the gene regulatory network of CEBPA-double mutant acute myeloid leukemia.

We identify the binding sites of mutated C/EBPa proteins in primary cells, we show that C/EBPa, AP-1 factors and RUNX1 colocalize and are required for AML maintenance, and we employ single cell experiments to link important network nodes to the specific differentiation trajectory from leukemic stem to blast cells. Taken together, our study provides an important resource which predicts the specific therapeutic vulnerabilities of this AML subtype in human cells.

Pubmed   Journal   ReadQx 

In vivo PDX CRISPR/Cas9 screens reveal mutual therapeutic targets to overcome heterogeneous acquired chemo-resistance.

Accordingly, venetoclax re-sensitized derivative tumors towards chemotherapy, despite genomic heterogeneity, demonstrating direct translatability of the approach. Hence, despite the presence of multiple resistance-associated genomic alterations, effective rescue treatment for polychemotherapy-resistant tumors can be identified using functional testing in preclinical models.

Pubmed   Journal   ReadQx 

Inhibition of USP1 reverses the chemotherapy resistance through destabilization of MAX in the relapsed/refractory B-cell lymphoma.

Moreover, pimozide showed a synergetic effect with etoposide, a chemotherapy drug, in cell and mouse models of rituximab/chemotherapy resistant DLBCL. Our study highlights the critical role of USP1 in the rituximab/chemotherapy resistance of DLBCL through deubiquitylating MAX, and provides a novel therapeutic strategy for rituximab/chemotherapy resistant DLBCL.

Pubmed   Journal   ReadQx 

Loss of bisecting GlcNAcylation on MCAM of bone marrow stoma determined pro-tumoral niche in MDS/AML.

MCAM on stromal cell surface with reduced bisecting GlcNAc bound strongly to CD13 on myeloid cells, activated responding ERK signaling, and thereby promoted myeloid cell growth. Our findings, taken together, suggest a novel mechanism whereby MDS/AML clonal cells generate a self-permissive niche by modifying glycosylation level of stromal cells.

Pubmed   Journal   ReadQx 

mTOR inhibition amplifies the anti-lymphoma effect of PI3Kß/d blockage in diffuse large B-cell lymphoma.

Collectively, our study reveals that subsets of DLBCLs are addicted to PI3Kß/d signaling and thus identifies a previously unappreciated role of the PI3Kß isoform in DLBCL survival. Furthermore, our data demonstrate that combined targeting of PI3Kß/d and mTOR is effective in al major DLBCL subtypes supporting the evaluation of this strategy in a clinical trial setting.

Pubmed   Journal   ReadQx 

Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma.

The presence of =2 of these factors was associated with inferior OS compared to =1 (56% vs 19%). In this largest analysis to date of patients who progressed or relapsed after CD19-CAR-T, survival is poor, though novel agents such as polatuzumab and lenalidomide may have hold promise.

Pubmed   Journal   ReadQx 


Reviews&Editorials

Plenty of the editorials are available as full text through the publisher website using the provided link

Ann Oncol

COP27 Climate Change Conference: urgent action needed for Africa and the world.

It is highly unjust that the most impacted nations have contributed the least to global cumulative emissions, which are driving the climate crisis and its increasingly severe effects. North America and Europe have contributed 62% of carbon dioxide emissions since the Industrial Revolution, whereas Africa has contributed only 3% (14).

Pubmed   Journal   ReadQx 

Blood

AML gets upSET when its dietary needs are unMet.

Pubmed   Journal   ReadQx 

Giving alloHSCT a needed LIF(t).

Pubmed   Journal   ReadQx 

RBC, heal thyself: PK activators in SCD.

Pubmed   Journal   ReadQx 

Transferrin-induced thrombosis in hypoxia.

Pubmed   Journal   ReadQx 

CA Cancer J Clin

Cancer statistics for American Indian and Alaska Native individuals, 2022: Including increasing disparities in early onset colorectal cancer.

These findings highlight the need for more effective strategies to reduce the prevalence of chronic oncogenic infections and improve access to high-quality cancer screening and treatment for AIAN individuals. Mitigating the disparate burden will require expanded financial support of tribal health care as well as increased collaboration and engagement with this marginalized population.

Pubmed   Journal   ReadQx 

J Hematol Oncol

Natural killer cells in clinical development as non-engineered, engineered, and combination therapies.

Additionally, the competitive landscape and business field is presented. This review offers a comprehensive overview of the effort driven by biotech and pharmaceutical companies and by academic centers to bring NK cell therapies to pivotal clinical trial stages and to market authorization.

Pubmed   Journal   ReadQx 

Lancet Haematol

Iron deficiency anaemia-an ongoing challenge.

Pubmed   Journal   ReadQx 


Miscellaneous

misc publications eg case reports, tools of the trade, images of the month, etc…

Am J Hematol

CAR T cell-driven cerebrospinal fluid cytokine storm with confounding neurological picture in chemorefractory primary cardiac lymphoma.

Pubmed   Journal   ReadQx 

Blood

Efficacy of tixagevimab-cilgavimab in preventing SARS-CoV-2 for patients with B-cell malignancies.

Pubmed   Journal   ReadQx 

F9 mutations causing deletion beyond serine protease domain confer higher risk for inhibitor development in hemophilia B.

Pubmed   Journal   ReadQx 

Ipilimumab plus decitabine for patients with MDS or AML in post-transplant or transplant naïve settings.

Pubmed   Journal   ReadQx 

Neutrophil-specific depletion of gasdermin D does not protect against sepsis.

Pubmed   Journal   ReadQx 

Platelet satellitism in immune thrombocytopenic purpura.

Pubmed   Journal   ReadQx 

Progressive Multifocal Leukoencephalopathy in Patients Treated With Chimeric Antigen Receptor T-Cells.

Pubmed   Journal   ReadQx 

Blood Adv

"Cord Blood Power" and "What is Success after BMT"?

Pubmed   Journal   ReadQx 

Buettner R, Morales C, Caserta E, et al. Leflunomide regulates c-Myc expression in myeloma cells through PIM targeting. Blood Adv. 2019;3(7):1027-1032.

Pubmed   Journal   ReadQx 

Chemical degradation of BTK/TEC as a novel approach to inhibit platelet function.

Pubmed   Journal   ReadQx 

Curing CLL: one clone at a time.

Pubmed   Journal   ReadQx 

Megakaryocyte buds are distinct from microvesicles and likely to represent platelet precursors.

Pubmed   Journal   ReadQx 

CA Cancer J Clin

Colonoscopies for patients aged 45-49 years yield positive results.

Pubmed   Journal   ReadQx 

Sustained weight loss may reduce cancer risk.

Pubmed   Journal   ReadQx 

Lancet Haematol

Burning out-whose responsibility is it?

Pubmed   Journal   ReadQx 

Isolated IgG4-related disease of the left maxillary antrum.

Pubmed   Journal   ReadQx 

Maximising response depth is important in multiple myeloma.

Pubmed   Journal   ReadQx 

Place-of-care manufacturing of gene therapies.

Pubmed   Journal   ReadQx 

Rahul Bhargava: making bone marrow transplantation accessible in India.

Pubmed   Journal   ReadQx 

Leukemia

Discriminating activities of DEAD-Box Helicase 41 from myeloid malignancy-associated germline variants by genetic rescue.

Pubmed   Journal   ReadQx 

Frequency and prognostic implications of KMT2A rearrangements in children with precursor B-cell lymphoma.

Pubmed   Journal   ReadQx 

How T-lymphoblastic leukemia can be classified based on genetics using standard diagnostic techniques enhanced by whole genome sequencing.

Pubmed   Journal   ReadQx 

Thromb Haemost

Newborn and Pediatric Reference Intervals for Coagulation Assays Using Novel Reagents.

Pubmed   Journal   ReadQx 


Letters&Replies

Letters to the editors and authors’ replies

Am J Hematol

Efficacy of Front-line Ibrutinib versus Fludarabine, Cyclophosphamide and Rituximab (FCR) in Patients with CLL. A Retrospective Multicenter "Real-World" Study.

Pubmed   Journal   ReadQx 

Blood Cancer J

Assessing the role of venetoclax in combination with hypomethylating agents in higher risk myelodysplastic syndrome.

Pubmed   Journal   ReadQx   PMC

Survival trends in hematological malignancies in the Nordic countries through 50 years.

Pubmed   Journal   ReadQx   PMC

J Hematol Oncol

FIT-based risk-stratification model effectively screens colorectal neoplasia and early-onset colorectal cancer in Chinese population: a nationwide multicenter prospective study.

The risk-stratification model identified 73.5% CN, 82.6% ACN, and 93.6% CRC when guiding 52.7% individuals to receive colonoscopy and identified 55.8% early-onset ACNs and 72.7% early-onset CRCs with only 25.6% young individuals receiving colonoscopy. The risk-stratification model showed a good risk-stratification ability for CN and early-onset CRCs in Chinese population, including individuals with NSGS and young age.

Pubmed   Journal   ReadQx   PMC

Leukemia

Differences in classification schemata for myelodysplastic/myeloproliferative overlap neoplasms.

Pubmed   Journal   ReadQx